Lipoprotein metabolism can be conveniently, yet intensively, studied by injecting radiolabeled HDL, LDL, or VLDL into the blood stream and then carefully measuring its disappearance from the blood, along with the excretion of radioactive iodine as a breakdown product in the urine. To address some of these issues we are also recruiting identical (MZ) and fraternal (DZ) twins to estimate the extent of genetic control of many different phenotypes in humans. In twin studies, the difference in pair similarity between MZ and DZ twins indicates how much of the phenotype in genetically controlled. We aim to study lipoprotein levels and related parameters in MZ and DZ pairs on low and high fat diets under metabolic ward conditions to estimate the genetic control of lipoprotein levels on a fixed diet and the genetic control of diet response. Body composition studies include the use of DPX (Dual photon absorptiometry), which measures body bone mass and whole body bone density utilizing an x-ray source adding information on fat distribution. DPX and other body composition studies might explain in part the differences in lipoprotein levels not accounted for the genetic background. Lipolytic enzymes play an important role in lipoprotein metabolism which, in turn, appears to play a crucial role in the development of atherosclerosis. In studying the factors which influence lipoprotein levels and metabolism, it is frequently desirable to measure body lipolytic activity concurrently with other lipoprotein parameters. The two most important lipolytic enzymes are lipoprotein lipase (LPL) and hepatic endothelial lipase (HL), each of which is believed to determine in part the levels of the triglyceride-rich lipoproteins and high-density lipoproteins (HDL). Both of these enzymes normally do not circulate in the plasma, but are bound to the endothelial cells which line the blood vessels of the body. In order to study the activity of these enzymes in human subjects, it is necessary either to biopsy the appropriate organ or to release the enzymes from the vessel wall into the circulation and then sample the blood. Heparin is chemically similar to the portion of these enzymes that bind to the vessel wall. When injected briefly, heparin then competes for that binding and releases most of LPL and HL into the blood. An appropriately timed blood sample can then be assayed in vitro for lipolytic activity of each of the enzymes by relatively simple techniques. In addition, it has been suggested that chylomicrons or their remnants are atherogenic. Chylomicrons carry dietary cholesterol into the bloodstream and these particles are degraded by the enzyme lipoprotein lipase in contact with the endothelium. After chylomicron triglyceride hydrolysis, chylomicron remnants, which are enriched in cholesteryl ester, may enter the vessel wall directly for uptake by arterial smooth muscle cells. Alternatively, circulating chylomicron remnants may be taken up by monocyte macrophages prior to their normal clearance by the liver. In both cases, foam cells may result which could contribute to the early stages of athero- sclerotic lesions. Therefore, the absolute level of chylomicrons and their remnants and their residency time in plasma may correlate with atherosclerosis. Typical lipoprotein measurements are done 10-12 hours after eating. The post-prandial events related to chylomicron metabolism in most cases would be undetected by these measurements. Our goal is to develop and apply a test which can measure chylomicron and chylomicron remnant clearance to see if abnormalities in this process correlate with fasting lipoprotein abnormalities associated with premature atherosclerosis as well to study the genetic determinants of this process in healthy subjects.